Abstract
Lyme disease spirochetes demonstrate strain- and species-specific differences in tissue tropism. For example, the three major Lyme disease spirochete species, Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii, are each most commonly associated with overlapping but distinct spectra of clinical manifestations. Borrelia burgdorferi sensu stricto, the most common Lyme spirochete in the U.S., is closely associated with arthritis. The attachment of microbial pathogens to cells or to the extracellular matrix of target tissues may promote colonization and disease, and the Lyme disease spirochete encodes several surface proteins, including the decorin- and dermatan sulfate-binding adhesin DbpA, which vary among strains and have been postulated to contribute to strain-specific differences in tissue tropism. DbpA variants differ in their ability to bind to its host ligands and to cultured mammalian cells. To directly test whether variation in dbpA influences tissue tropism, we analyzed murine infection by isogenic B. burgdorferi strains that encode different dbpA alleles. Compared to dbpA alleles of B. afzelii strain VS461 or B. burgdorferi strain N40-D10/E9, dbpA of B. garinii strain PBr conferred the greatest decorin- and dermatan sulfate-binding activity, promoted the greatest colonization at the inoculation site and heart, and caused the most severe carditis. The dbpA of strain N40-D10/E9 conferred the weakest decorin- and GAG-binding activity, but the most robust joint colonization and was the only dbpA allele capable of conferring significant joint disease. Thus, dbpA mediates colonization and disease by the Lyme disease spirochete in an allele-dependent manner and may contribute to the etiology of distinct clinical manifestations associated with different Lyme disease strains. This study provides important support for the long-postulated model that strain-specific variations of Borrelia surface proteins influence tissue tropism.
Highlights
Lyme disease is distributed worldwide and is the most common arthropod-borne infectious disease in the United States [1,2,3]
The most common vector-borne disease in the United States, is caused by a bacterium, Borrelia burgdorferi. This bacterium infects the skin at the site of the tick bite and can spread to other tissues, such as the heart, joints or nervous system, causing carditis, arthritis or neurologic disease
We found that the strains colonized different tissues and caused different diseases, such as arthritis or carditis
Summary
Lyme disease is distributed worldwide and is the most common arthropod-borne infectious disease in the United States [1,2,3]. The causative agent is the spirochete Borrelia burgdorferi sensu lato, which includes B. burgdorferi sensu stricto, B. garinii, and B. afzelii [4] [5]. In the absence of antibiotic treatment, spirochetes may disseminate to multiple organs, including joints, the central nervous system, and the heart, resulting in diverse manifestations such as arthritis, neurological abnormalities, and carditis [2,6,7,8,9]. Lyme disease spirochetes demonstrate strain- and speciesspecific differences in tissue tropism. B. burgdorferi sensu stricto, most prevalent in the United States, B. garinii and B. afzelii, each more common in Europe [1,5], are genetically distinct and are associated with different typical chronic manifestations: B
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
